During learning and development, the level of synaptic input received by a cortical neuron may vary dramatically over time. Given a limited range of possible firing rates, how do neurons remain responsive to their inputs both when synaptic input is small and when it is large? We have demonstrated that one means available to pyramidal neurons to address this problem is to regulate their intrinsic excitability in response to changes in activity. In particular we found that neurons that had been deprived of activity for extended periods (days) fired more rapidly than did their control counterparts, and in response to smaller amounts of current. This change in excitability was mediated by a selective regulation of ionic conductances. This finding suggests that cortical neurons can remain responsive to their inputs in a changing environment by altering the function relating synaptic input to firing rate. Here I propose to use dissociated neurons grown on multielectrode arrays to investigate several issues raised by this earlier work: What aspect of activity controls this process? How sensitive is a neuron's intrinsic excitability to its level of activity? What are the implications of this novel form of plasticity for information transmission between neurons? The answers to these questions will help to elucidate the biological importance of this phenomenon to development and learning.